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Gastroenterology ; 160(5): 1647-1661, 2021 04.
Article in English | MEDLINE | ID: covidwho-1065985


BACKGROUND & AIMS: Gastrointestinal (GI) manifestations have been increasingly reported in patients with coronavirus disease 2019 (COVID-19). However, the roles of the GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We investigated how the GI tract is involved in SARS-CoV-2 infection to elucidate the pathogenesis of COVID-19. METHODS: Our previously established nonhuman primate (NHP) model of COVID-19 was modified in this study to test our hypothesis. Rhesus monkeys were infected with an intragastric or intranasal challenge with SARS-CoV-2. Clinical signs were recorded after infection. Viral genomic RNA was quantified by quantitative reverse transcription polymerase chain reaction. Host responses to SARS-CoV-2 infection were evaluated by examining inflammatory cytokines, macrophages, histopathology, and mucin barrier integrity. RESULTS: Intranasal inoculation with SARS-CoV-2 led to infections and pathologic changes not only in respiratory tissues but also in digestive tissues. Expectedly, intragastric inoculation with SARS-CoV-2 resulted in the productive infection of digestive tissues and inflammation in both the lung and digestive tissues. Inflammatory cytokines were induced by both types of inoculation with SARS-CoV-2, consistent with the increased expression of CD68. Immunohistochemistry and Alcian blue/periodic acid-Schiff staining showed decreased Ki67, increased cleaved caspase 3, and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these 2 types of inoculation with SARS-CoV-2 impaired the GI barrier and caused severe infections. CONCLUSIONS: Both intranasal and intragastric inoculation with SARS-CoV-2 caused pneumonia and GI dysfunction in our rhesus monkey model. Inflammatory cytokines are possible connections for the pathogenesis of SARS-CoV-2 between the respiratory and digestive systems.

COVID-19/transmission , Gastroenteritis/pathology , Gastrointestinal Tract/pathology , Lung/pathology , Animals , Bronchi/metabolism , Bronchi/pathology , COVID-19/immunology , COVID-19/metabolism , COVID-19/pathology , COVID-19 Nucleic Acid Testing , Caspase 3/metabolism , Cytokines/immunology , Disease Models, Animal , Gastric Mucosa , Gastroenteritis/metabolism , Gastroenteritis/virology , Gastrointestinal Tract/immunology , Gastrointestinal Tract/metabolism , Goblet Cells/pathology , Intestine, Small/metabolism , Intestine, Small/pathology , Ki-67 Antigen/metabolism , Lung/diagnostic imaging , Lung/immunology , Lung/metabolism , Macaca mulatta , Nasal Mucosa , RNA, Viral/isolation & purification , Random Allocation , Rectum/metabolism , Rectum/pathology , SARS-CoV-2 , Trachea/metabolism , Trachea/pathology
Sci Rep ; 10(1): 16007, 2020 09 29.
Article in English | MEDLINE | ID: covidwho-809120


Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a pandemic event in the world, it has not only caused huge economic losses, but also a serious threat to global public health. Many scientific questions about SARS-CoV-2 and Coronavirus disease (COVID-19) were raised and urgently need to be answered, including the susceptibility of animals to SARS-CoV-2 infection. Here we tested whether tree shrew, an emerging experimental animal domesticated from wild animal, is susceptible to SARS-CoV-2 infection. No clinical signs were observed in SARS-CoV-2 inoculated tree shrews during this experiment except the increasing body temperature particularly in female animals. Low levels of virus shedding and replication in tissues occurred in all three age groups. Notably, young tree shrews (6 months to 12 months) showed virus shedding at the earlier stage of infection than adult (2 years to 4 years) and old (5 years to 7 years) animals that had longer duration of virus shedding comparatively. Histopathological examine revealed that pulmonary abnormalities were the main changes but mild although slight lesions were also observed in other tissues. In summary, tree shrew is less susceptible to SARS-CoV-2 infection compared with the reported animal models and may not be a suitable animal for COVID-19 related researches. However, tree shrew may be a potential intermediate host of SARS-CoV-2 as an asymptomatic carrier.

Coronavirus Infections/veterinary , Host Specificity/physiology , Pandemics/veterinary , Pneumonia, Viral/veterinary , Tupaiidae/virology , Animals , Betacoronavirus , COVID-19 , Coronavirus Infections/pathology , Disease Susceptibility/veterinary , Disease Susceptibility/virology , Female , Male , Pneumonia, Viral/pathology , SARS-CoV-2 , Viral Load , Virus Shedding/physiology
BMC Infect Dis ; 20(1): 549, 2020 Jul 29.
Article in English | MEDLINE | ID: covidwho-684717


BACKGROUND: We aimed to report the epidemiological and clinical characteristics of hospitalized patients with coronavirus disease-19 (COVID-19) in Zengdu District, Hubei Province, China. METHODS: Clinical data on COVID-19 inpatients in Zengdu Hospital from January 27 to March 11, 2020 were collected; this is a community hospital in an area surrounding Wuhan and supported by volunteer doctors. All hospitalized patients with COVID-19 were included in this study. The epidemiological findings, clinical features, laboratory findings, radiologic manifestations, and clinical outcomes of these patients were analyzed. The patients were followed up for clinical outcomes until March 22, 2020. Severe COVID-19 cases include severe and critical cases diagnosed according to the seventh edition of China's COVID-19 diagnostic guidelines. Severe and critical COVID-19 cases were diagnosed according to the seventh edition of China's COVID-19 diagnostic guidelines. RESULTS: All hospitalized COVID-19 patients, 276 (median age: 51.0 years), were enrolled, including 262 non-severe and 14 severe patients. The proportion of patients aged over 60 years was higher in the severe group (78.6%) than in the non-severe group (18.7%, p < 0.01). Approximately a quarter of the patients (24.6%) had at least one comorbidity, such as hypertension, diabetes, or cancer, and the proportion of patients with comorbidities was higher in the severe group (85.7%) than in the non-severe group (21.4%, p < 0.01). Common symptoms included fever (82.2% [227/276]) and cough (78.0% [218/276]). 38.4% (106/276) of the patients had a fever at the time of admission. Most patients (94.9% [204/276]) were cured and discharged; 3.6% (10/276) deteriorated to a critical condition and were transferred to another hospital. The median COVID-19 treatment duration and hospital stay were 14.0 and 18.0 days, respectively. CONCLUSIONS: Most of the COVID-19 patients in Zengdu had mild disease. Older patients with underlying diseases were at a higher risk of progression to severe disease. The length of hospital-stay and antiviral treatment duration for COVID-19 were slightly longer than those in Wuhan. This work will contribute toward an understanding of COVID-19 characteristics in the areas around the core COVID-19 outbreak region and serve as a reference for decision-making for epidemic prevention and control in similar areas.

Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Length of Stay/statistics & numerical data , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Adolescent , Adult , COVID-19 , Child , Child, Preschool , China/epidemiology , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Cough/epidemiology , Female , Fever/epidemiology , Humans , Hypertension/epidemiology , Infant , Infant, Newborn , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Retrospective Studies , SARS-CoV-2 , Treatment Outcome , Young Adult